| First Author | Uchio-Yamada K | Year | 2020 |
| Journal | Am J Physiol Renal Physiol | Volume | 318 |
| Issue | 6 | Pages | F1520-F1530 |
| PubMed ID | 32390516 | Mgi Jnum | J:298141 |
| Mgi Id | MGI:6469845 | Doi | 10.1152/ajprenal.00055.2020 |
| Citation | Uchio-Yamada K, et al. (2020) Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier. Am J Physiol Renal Physiol 318(6):F1520-F1530 |
| abstractText | Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies have revealed that Tns2-deficient mice exhibit defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by Tns2 deficiency remains unidentified. Here, we aimed to determine the role of Tns2 using newborn Tns2-deficient mice and murine primary podocytes. Ultrastructural analysis revealed that developing glomeruli during postnatal nephrogenesis exhibited abnormal GBM processing due to ectopic laminin-alpha2 accumulation followed by GBM thickening. In addition, analysis of primary podocytes revealed that Tns2 deficiency led to impaired podocyte-GBM interaction and massive expression of laminin-alpha2 in podocytes. Our study suggests that weakened podocyte-GBM interaction due to Tns2 deficiency causes increased mechanical stress on podocytes by continuous daily filtration after birth, resulting in stressed podocytes ectopically producing laminin-alpha2, which interrupts GBM processing. We conclude that Tns2 plays important roles in the podocyte-GBM interaction and maintenance of the glomerular filtration barrier. |
